Aortic valve stenosis is a common cardiac disease resulting in approximately 65,000 aortic valve replacement surgeries in the United States annually. Aortic valve stenosis can occur via several etiologies including rheumatic disease, congenital and degenerative calcific stenosis. In developing countries, rheumatic fever results in thickening and progressive immobility of the valve tissues. Calcific disease accounts for almost all of the cases of aortic stenosis in the United States and in developed nations where rheumatic disease is rare.
Over time, a build up of calcium can occur in the annulus of the valve, along the leaflet cusps and on or within the leaflets. This calcific material such as nodular calcific deposits may be superimposed on an underlying fibrotic aortic valve leaflet or calcific deposits may be diffusely distributed throughout the body (spongiosa) of the aortic valve leaflets. Although distribution and type of deposits may differ depending on valve geometry (bicuspid, tricuspid), the deposits generally contribute to leaflet immobility, thickening and other pathologies that lead to degenerative valve function. The presence and progression of this disease leads to a decreased functional area of the valve and dramatically reduced cardiac output.
In the late 1980s and early 1990s balloon dilation of the aortic valve, or valvuloplasty, became a popular therapy for aortic valve stenosis. Dilation of the aortic valve using large angioplasty balloons from either an antegrade (transeptal) or retrograde (aortic) approach resulted in improvements in left ventricular ejection fractions (increased cardiac output), decreases in pressure gradients across the valve, and increases in valve cross-sectional area. Various valvuloplasty balloon designs and other approaches, including energy based therapies, have been disclosed in U.S. Pat. No. 3,667,474 Lapkin, U.S. Pat. No. 4,484,579 Meno, U.S. Pat. No. 4,787,388 Hoffman, U.S. Pat. No. 4,777,951 Cribier, U.S. Pat. No. 4,878,495 and U.S. Pat. No. 4,796,629 to Grayzel, U.S. Pat. No. 4,819,751 Shimada, U.S. Pat. No. 4,986,830 Owens, U.S. Pat. No. 5,443,446 and U.S. Pat. No. 5,295,958 to Schturman, U.S. Pat. No. 5,904,679 Clayman, U.S. Pat. No. 5,352,199 and U.S. Pat. No. 6,746,463 to Tower, the disclosures of which are expressly incorporated herein by reference.
In addition, various surgical approaches to de-calcify the valve lesions were attempted utilizing ultrasonic devices to debride or obliterate the calcific material. Such devices include the CUSA Excel™ Ultrasonic Surgical Aspirator and handpieces (23 kHz and 36 kHz, Radionics, TYCO Healthcare, Mansfield, Mass.). Further work, approaches and results have been documented in “Contrasting Histoarchitecture of calcified leaflets from stenotic bicuspid versus stenotic tricuspid aortic valves,” Journal of American College of Cardiology 1990 April; 15(5):1104-8, Ultrasonic Aortic Valve Decalcification: Serial Doppler Echocardiographic Follow Up” Journal of American College of Cardiology 1990 September; 16(3): 623-30, and “Percutaneous Balloon Aortic Valvuloplasty: Antegrade Transseptal vs. Conventional Retrograde Transarterial Approach” Catheterization and Cardiovascular interventions 64:314-321 (2005), the disclosures of which are expressly incorporated by reference herein.
Devices and techniques have suffered from only a modest ability to increase valve cross-sectional area, however. For instance, many studies showed that a pre-dilatation area of about 0.6 cm2 could be opened to only between about 0.9 to about 1.0 cm2. It would be desirable to open such a stenosis to an area closer to about 1.2 to about 1.5 cm2. In addition to opening the cross-sectional area, it may be desirable to treat the leaflets and surrounding annulus to remove calcific deposits that stiffen the valve, impair flow dynamics, and otherwise degenerate valve function. Toward this end, other techniques such as direct surgical ultrasonic debridement of calcium deposits have had some success, but required an open surgical incision, thereby increasing the risk to the patient.
Although balloon dilatation offered patients a viable, less invasive alternative, it fell into disfavor in the early to mid 1990s primarily as a result of rapid restenosis of the valve post treatment. At six months, reports of restenosis rates were commonly in excess of 70-80%. Today, balloon valvuloplasty is primarily reserved for palliative care in elderly patients who are not candidates for surgical replacement due to comorbid conditions.
Recent clinical focus on technologies to place percutaneous valve replacement technologies have also caused some to revisit valvuloplasty and aortic valve repair. Corazon, Inc. is developing a system which isolates the leaflets of the aortic valve so that blood flow through the center of the device is preserved while calcium dissolving or softening agents are circulated over and around the leaflets. See for example, United States Patent Application Publication 2004/0082910, the disclosure of which is expressly incorporated herein by reference. The hope is that reducing the stiffness of the leaflets by softening the calcium will allow for more normal functioning of the valve and increased cardiac output. The system is complex, requires upwards of 30 minutes of softening agent exposure time, and has resulted in complete AV block and emergency pacemaker implantation in some patients.
In addition, other technologies have been documented to address aortic stenosis in various ways. U.S. Patent Application Publication 2005/007219 to Pederson discloses balloon materials and designs, as well as ring implants for use in valvuloplasty and treatment of aortic stenosis, the disclosure of which is expressly incorporated herein by reference. Further, Dr. Pederson recently presented initial results of the RADAR study for aortic valve stenosis therapy. This study combines traditional balloon valvuloplasty with external beam radiation to try to prevent the restenosis which occurs post-dilatation. While radiation therapy has been shown to have a positive impact on restenosis in coronary angioplasty, the methods employed in the RADAR study require that the patient undergo a minimum of 4-6 separate procedures, the initial valvuloplasty plus 3-5 separate radiation therapy sessions. These radiation therapy sessions are similar to those used for radiation treatment for cancer.
Over the past three years, dramatic advances in the prevention of restenosis after coronary balloon angioplasty and stenting have been made by the introduction of drug-eluting stents by companies like Boston Scientific and Johnson & Johnson. These devices deliver a controlled and prolonged dose of antiproliferative agents to the wall of the coronary artery in order to manage the sub-acute wound healing and prevent the long-term hyperproliferative healing response that caused restenosis in bare metal stents or in stand-alone angioplasty. Furthermore, various advances have been made on the administration of anti-calcification drugs, including ACE inhibitors, statins, and angiotensins, specifically angiotensin II, as detailed in United States Patent Application Publication 2004/0057955, the disclosure of which is expressly incorporated herein by reference.
While the conventional methods have proven to be reasonably successful, the problem of aortic valve stenosis and subsequent restenosis after valvuloplasty or other intervention still requires better solutions. The present invention provides various devices and methods that create more effective treatments for aortic stenosis and prevent or reduce the incidence and/or severity of aortic restenosis. In addition, the present inventions provides methods and devices for decalcification or debridement of aortic stenosis, either as a stand alone therapy or in conjunction with conventional techniques, such as traditional valvuloplasty, stenting, valve repair, and percutaneous or surgical valve replacement.